Variant 5-116446797-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_020796.5(SEMA6A):c.2909A>C(p.Gln970Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00573 in 1,613,124 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0042 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0059 ( 31 hom. )

Consequence

SEMA6A
NM_020796.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.73

Variant links:

Genes affected

SEMA6A (HGNC:10738): (semaphorin 6A) Predicted to enable identical protein binding activity; signaling receptor binding activity; and transmembrane signaling receptor activity. Involved in cellular response to vascular endothelial growth factor stimulus; negative regulation of cell adhesion involved in sprouting angiogenesis; and negative regulation of signal transduction. Predicted to be integral component of membrane. Predicted to be active in extracellular space. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SEMA6A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007560551).

BP6

Variant 5-116446797-T-G is Benign according to our data. Variant chr5-116446797-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 718147.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 31 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA6A	NM_020796.5 linkuse as main transcript	c.2909A>C	p.Gln970Pro	missense_variant	19/19	ENST00000343348.11	NP_065847.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA6A	ENST00000343348.11 linkuse as main transcript	c.2909A>C	p.Gln970Pro	missense_variant	19/19	1	NM_020796.5	ENSP00000345512	P4	Q9H2E6-1

Frequencies

GnomAD3 genomes

AF:

0.00421

AC:

640

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00125

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.00720

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00584

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00691

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00470

AC:

1159

AN:

246662

Hom.:

AF XY:

0.00464

AC XY:

622

AN XY:

133916

show subpopulations

Gnomad AFR exome

AF:

0.00119

Gnomad AMR exome

AF:

0.00146

Gnomad ASJ exome

AF:

0.00722

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000986

Gnomad FIN exome

AF:

0.00771

Gnomad NFE exome

AF:

0.00720

Gnomad OTH exome

AF:

0.00334

GnomAD4 exome

AF:

0.00589

AC:

8600

AN:

1460838

Hom.:

Cov.:

AF XY:

0.00582

AC XY:

4231

AN XY:

726622

show subpopulations

Gnomad4 AFR exome

AF:

0.000747

Gnomad4 AMR exome

AF:

0.00159

Gnomad4 ASJ exome

AF:

0.00801

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000975

Gnomad4 FIN exome

AF:

0.00786

Gnomad4 NFE exome

AF:

0.00671

Gnomad4 OTH exome

AF:

0.00545

GnomAD4 genome

AF:

0.00420

AC:

640

AN:

152286

Hom.:

Cov.:

AF XY:

0.00396

AC XY:

295

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00125

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.00720

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00584

Gnomad4 NFE

AF:

0.00691

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00659

Hom.:

Bravo

AF:

0.00379

TwinsUK

AF:

0.00405

AC:

ALSPAC

AF:

0.00908

AC:

ESP6500AA

AF:

0.00120

AC:

ESP6500EA

AF:

0.00733

AC:

ExAC

AF:

0.00445

AC:

539

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 08, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2023	SEMA6A: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.16

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.032

.;T;T;.;.

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.91

.;D;D;D;.

M_CAP

Benign

0.013

MetaRNN

Benign

0.0076

T;T;T;T;T

MetaSVM

Benign

-0.95

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-2.2

N;N;N;N;N

REVEL

Benign

0.23

Sift

Uncertain

0.012

D;D;D;D;D

Sift4G

Benign

0.15

T;T;D;D;T

Polyphen

0.96, 0.94

.;.;D;P;.

Vest4

0.59

MVP

0.41

MPC

0.71

ClinPred

0.026

GERP RS

4.3

gMVP

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over